دورية أكاديمية
أعرض في EDS

Aβ25-35-induced autophagy and apoptosis are prevented by the CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR signaling hub.

التفاصيل البيبلوغرافية
العنوان: Aβ25-35-induced autophagy and apoptosis are prevented by the CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR signaling hub.
المؤلفون: Ji Y; Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, PR China., Ren J; Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, PR China., Qian Y; Beijing Jishuitan Hospital, Peking University Fourth School of Clinical Medicine, Beijing, PR China., Li J; Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, PR China., Liu H; Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, PR China., Yao Y; Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, PR China., Sun J; Department of Physiology, Jilin University, Changchun, Jilin, PR China., Khanna R; Department of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.; Pain and Addiction Therapeutics (PATH) Collaboratory, College of Medicine, University of Florida, Gainesville, Florida, United States of America., Sun L; Department of Neurology and Neuroscience Center, The First Hospital, Jilin University, Changchun, Jilin, PR China.
المصدر: PloS one [PLoS One] 2024 Sep 26; Vol. 19 (9), pp. e0309794. Date of Electronic Publication: 2024 Sep 26 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Apoptosis*/drug effects , Amyloid beta-Peptides*/metabolism , Amyloid beta-Peptides*/toxicity , Autophagy*/drug effects , TOR Serine-Threonine Kinases*/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Kinase*/metabolism , Peptide Fragments*/toxicity , Peptide Fragments*/metabolism , Signal Transduction*/drug effects , AMP-Activated Protein Kinases*/metabolism , Intercellular Signaling Peptides and Proteins*/metabolism , Nerve Tissue Proteins*/metabolism, Humans ; Cell Line, Tumor ; Calcium/metabolism
مستخلص: We previously reported that the peptide ST2-104 (CBD3, for Ca2+ channel-binding domain 3), derived from the collapsin response mediator protein 2 (CRMP2)-a cytosolic phosphoprotein, protects neuroblastoma cells against β-amyloid (Aβ) peptide-mediated toxicity through engagement of a phosphorylated CRMP2/NMDAR pathway. Abnormal aggregation of Aβ peptides (e.g., Aβ25-35) leads to programmed cell death (apoptosis) as well autophagy-both of which contribute to Alzheimer's disease (AD) progression. Here, we asked if ST2-104 affects apoptosis and autophagy in SH-SY5Y neuroblastoma challenged with the toxic Aβ25-35 peptide and subsequently mapped the downstream signaling pathways involved. ST2-104 protected SH-SY5Y cells from death following Aβ25-35 peptide challenge by reducing apoptosis and autophagy as well as limiting excessive calcium entry. Cytotoxicity of SHY-SY5Y cells challenged with Aβ25-35 peptide was blunted by ST2-104. The autophagy activator Rapamycin blunted the anti-apoptotic activity of ST2-104. ST2-104 reversed Aβ25-35-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKβ). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through a CaMKKβ/AMPK/mTOR signaling hub. These findings identify a mechanism whereby, in the face of Aβ25-35, the concerted actions of ST2-104 leads to a reduction in intracellular calcium overload and inhibition of the CaMKKβ/AMPK/mTOR pathway resulting in attenuation of autophagy and cellular apoptosis. These findings define a mechanistic framework for how ST2-104 transduces "outside" (calcium channels) to "inside" signaling (CaMKKβ/AMPK/mTOR) to confer neuroprotection in AD.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Amyloid beta-Peptides)
0 (amyloid beta-protein (25-35))
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
0 (Peptide Fragments)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
0 (Intercellular Signaling Peptides and Proteins)
0 (collapsin response mediator protein-2)
0 (Nerve Tissue Proteins)
EC 2.7.1.1 (MTOR protein, human)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20240926 Date Completed: 20240926 Latest Revision: 20240928
رمز التحديث: 20240928
مُعرف محوري في PubMed: PMC11426444
DOI: 10.1371/journal.pone.0309794
PMID: 39325788
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0309794